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Basic Science Investigations |
1 Nuclear Medicine, Department of Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
2 Department of Radiation Oncology, Brigham and Women’s Hospital/Dana Farber Cancer Institute and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
3 IDEC Pharmaceuticals Corporation, San Diego, California
4 Department of Nuclear Medicine, Northwestern University, Chicago, Illinois
5 Department of Nuclear Medicine, MD Anderson Cancer Center, Houston, Texas
6 Oak Ridge Associated Universities, Knoxville, Tennessee
7 Vanderbilt University, Nashville, Tennessee
8 Division of Hematology, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
Ibritumomab tiuxetan is an anti-CD20 murine IgG1 
monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates 111In for imaging or dosimetry and 90Y for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of 90Y-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL) were combined and assessed for correlations with toxicity data. Methods: Data from 179 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be 
100,000 cells/mm3 for the reduced 90Y-ibritumomab tiuxetan administered dose (7.4–11 MBq/kg [0.2–0.3 mCi/kg]) or 150,000 cells/mm3 for the standard 90Y-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) 111In-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dose of 7.4–15 MBq/kg (0.2–0.4 mCi/kg) 90Y-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m2 rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for 90Y in blood and major organs were estimated from 111In biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow. Results: Median radiation absorbed doses for 90Y were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood effective half-life, or blood AUC. Conclusion: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with 90Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.
Key Words: dosimetry • radioimmunotherapy • 90Y-ibritumomab tiuxetan • rituximab
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